Sulfenylnitrene-Mediated Nitrogen-Atom Insertion into Pyrroles, Indoles, and Imidazoles

12 February 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

In this study, we harness the distinct reactivity of sulfenylnitrenes, which insert a single nitrogen atom to transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, and triazines, respectively. Our additive-free method for skeletal editing employs easily accessible, benchtop-stable sulfenylnitrene precursors as a source of a single nitrogen atom. This chemical approach is compatible with free pyrroles, indoles, and imidazoles with diverse functional groups, including oxidation-sensitive functionalities like phenol and thioether. Additionally, this approach facilitates the selective incorporation of a single nitrogen atom into various natural products, amino acids, and pharmaceuticals. Furthermore, we have conducted mechanistic studies and explored regioselectivity outcomes through DFT calculations.

Keywords

Scaffold Hopping
Skeletal Editing
Late Stage Functionalization
Sulfenylnitrenes
Nitrogen Atom Insertion
Single Atom Logic
Nitrene
Ring Expansion
N-Heterocycles

Supplementary materials

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Supporting Information (SI)
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Supporting Information for Publication, which includes the synthetic protocols, computational studies, and NMR spectra.
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Comment number 1, Marvin Lübcke: Feb 13, 2024, 20:12

Structures 2q and 2q‘ are mistakenly drawn identical. Nice work!

Response,
Indrajeet Sharma :
Feb 15, 2024, 14:20

Marvin: Thank you very much for pointing this out. We appreciate your valuable feedback. We will fix this error in the version 2.